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Crovalimab, a novel C5 inhibitor, allows for low-volume, every-4- week, subcutaneous self-administration. COMMODORE 1 (NCT04432584) is a phase 3, global, randomized trial evaluating crovalimab versus eculizumab in C5 inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). Adults with lactate dehydrogenase ≤1.5 × upper limit of normal and receiving approved eculizumab doses for ≥24 weeks were randomized 1:1 to receive crovalimab (weight-based tiered dosing) or continue eculizumab. The original primary study objective was efficacy; however, given the evolving treatment landscape, target recruitment was not met, and all efficacy endpoints became exploratory, with safety as the new primary objective. Exploratory efficacy endpoints included transfusion avoidance, hemolysis control, breakthrough hemolysis, hemoglobin stabilization, FACIT-Fatigue score, and patient preference (crovalimab vs. eculizumab). Eighty-nine patients were randomized (45 to crovalimab; 44 to eculizumab). During the 24-week primary treatment period, adverse events (AEs) occurred in 77% of patients receiving crovalimab and 67% receiving eculizumab. No AEs led to treatment withdrawal or death, and no meningococcal infections occurred. 16% of crovalimab-treated patients had transient immune complex reactions (also known as Type III hypersensitivity events), an expected risk when switching between C5 inhibitors that bind to different C5 epitopes; most were mild/moderate and all resolved without treatment modification. Crovalimab-treated patients had sustained terminal complement activity inhibition, maintained disease control, and 85% preferred crovalimab over eculizumab. Together with phase 3 COMMODORE 2 results in complement inhibitor-naive patients, these data support crovalimab's favorable benefit-risk profile. Crovalimab is a new C5 inhibitor for PNH that is potentially less burdensome than existing therapies for this lifelong disease.

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Importance: On September 20, 2017, one of the most destructive hurricanes in US history made landfall in Puerto Rico. Anecdotal reports suggest that many persons with kidney failure left Puerto Rico after Hurricane Maria; however, empirical estimates of migration and health outcomes for this population are scarce. Objective: To assess the changes in migration and mortality among patients with kidney failure in need of dialysis treatment in Puerto Rico after Hurricane Maria. Design, Setting, and Participants: This cross-sectional study used an interrupted time-series design of 6-month mortality rates and migration of 11 652 patients who received hemodialysis or peritoneal dialysis care in Puerto Rico before Hurricane Maria (before October 1, 2017) and/or during and after Hurricane Maria (on/after October 1, 2017). Data analyses were performed from February 12, 2019, to June 16, 2022.. Main Outcomes and Measures: Number of unique persons dialyzed in Puerto Rico per quarter; receipt of dialysis treatment outside Puerto Rico per quarter; and 6-month mortality rate per person-quarter for all persons undergoing dialysis. Exposures: Hurricane Maria. Results: The entire study sample comprised 11 652 unique persons (mean [SD] age, 59 [14.7] years; 7157 [61.6%] men and 4465 [38.4%] women; 10 675 [91.9%] Hispanic individuals). There were 9022 patients with kidney failure and dialysis treatment before and 5397 patients after Hurricane Maria. Before the hurricane, the mean quarterly number of unique persons dialyzed in Puerto Rico was 2834 per quarter (95% CI, 2771-2897); afterwards it dropped to 261 (95% CI, -348 to -175; relative change, 9.2%). The percentage of persons who had 1 or more dialysis sessions outside of Puerto Rico in the next quarter following a previous dialysis in Puerto Rico was 7.1% before Hurricane Maria (95% CI, 4.8 to 9.3). There was a significant increase of 5.8 percentage points immediately after the hurricane (95% CI, 2.7 to 9.0). The 6-month mortality rate per person-quarter was 0.08 (95% CI, 0.08 to 0.09), and there was a nonsignificant increase in level of mortality rates and a nonsignificant decreasing trend in mortality rates. Conclusions and Relevance: The findings of this cross-sectional study suggest there was a significant increase in the number of people receiving dialysis outside of Puerto Rico after Hurricane Maria. However, no significant differences in mortality rates before and after the hurricane were found, which may reflect disaster emergency preparedness among dialysis facilities and the population with kidney failure, as well as efforts from other stakeholders.

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OBJECTIVES: Studies examining the effects of statins after acute myocardial infarction (AMI) excluded frail older adults, especially nursing home (NH) residents, and few examined functional outcomes. Older NH residents may benefit less from statins and be particularly susceptible to adverse drug events like myopathy-related functional decline. We evaluated the effects of statins on 1-year functional decline, rehospitalization, and death in NH residents. DESIGN: We conducted a retrospective cohort study using 2007-2010 linked national data from Minimum Data Set (MDS) assessments, Medicare claims, and Online Survey Certification and Reporting System records. SETTING AND PARTICIPANTS: We included US NH residents 65 years and older who were statin nonusers, were hospitalized for AMI between May 2007 and March 2010, and returned to the NH. MEASURES: Outcomes were functional decline, death, and rehospitalization in the first year after post-AMI NH admission. New statin users were 1:1 propensity-score matched to nonusers to adjust for 92 characteristics. We estimated hazard ratios (HRs) and restricted mean survival time differences with 95% confidence intervals (CIs) comparing individuals who did vs did not initiate statin therapy after AMI hospitalization. RESULTS: Propensity-score matching yielded a cohort of 5440 residents. Mean age was 83 years and 69% were female. Statin use was associated with a reduction in mortality (HR 0.80, 95% CI 0.73-0.87), corresponding to a mean of 15.9 (95% CI 9.9-22.0) days of extended life expectancy. No overall differences in rehospitalization (HR 1.06, 95% CI 0.98-1.14) or functional decline (HR 1.00, 95% CI 0.88-1.14) were observed. CONCLUSIONS AND IMPLICATIONS: Statins may reduce 1-year mortality by 20% without affecting function among older NH residents who wish to live longer after AMI. During shared decision making with these patients or their representatives, clinicians should consider communicating that the average benefit of statins is 16 days of additional survival over 1 year.

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OBJECTIVE: To examine the association between food insecurity and body mass index (BMI) from early adolescence to adulthood. STUDY DESIGN: Growth curve analyses were performed. Sex differences were examined by conducting the analyses separately by sex. Ten data points were examined over a 16-year period from age 15 to 31 years. Data were obtained from the Family Transitions Project, a longitudinal study of 559 adolescents and their families that was initiated in 1989 in the Midwest. Primarily rural, non-Hispanic whites were selected based on the economic farm crisis. We examined participants from adolescence to adulthood from 1991 through 2007. Measures included a 2-item food insecurity construct and BMI as indicated by self-reported height and weight from adolescence through middle adulthood. These associations were analyzed using prospective growth curve modeling. RESULTS: Our analyses indicated a general increase in BMI with age, whereas food insecurity declined over time. Higher levels of food insecurity at age 15 years led to a more rapid increase in BMI. Finally, a positive relationship was found between the changes in food insecurity and BMI over time. These associations held only for females. CONCLUSION: Our results argue for increasing access to food during key developmental periods such as early adolescence, which could help reduce the long-term implications for health, particularly BMI in girls.

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